Emerging data suggest that low-level exposure to metals such as manganese and arsenic may result in adverse neurodevelopmental outcomes. Environmental manganese and arsenic are elevated in industrial regions as well as geographic locations with naturally high background levels. Despite the known susceptibility of the developing fetus and young children to environmental insults, epidemiological investigations of prenatal and early childhood exposure to these toxic metals are sparse. A few small studies have recently found decreased cognitive performance among children with increased exposure to manganese and arsenic without identifying an exposure threshold for adverse effects. The proposed project builds on the Study of C8 and Neurobehavioral Development among Children from the C8 Health Project. The Study of C8 and Neurobehavioral Development is a cohort study of approximately 550 children age 6 to 12 years designed to examine the association between perfluorinated compound exposure and child neurobehavioral development as evaluated through a comprehensive battery of neurobehavioral instruments. In addition, the biological mother is interviewed about the child's behavior, prenatal and early life experiences that may affect the child's development, and the child's home environment. Hair samples from the child are collected and stored in a biorepository. For the proposed project, we will measure biomarkers of exposure to manganese and arsenic in the stored hair samples and use the extensive neurobehavioral development outcome data already being collected to assess the effect of exposure to manganese and arsenic on child neurobehavioral development. Additionally, we will assess the joint effect of exposure to manganese and arsenic on neurobehavioral development because there is new epidemiological evidence that manganese and arsenic may act synergistically to negatively impact child neurodevelopment. Lastly, we will examine the temporal variability of biomarkers of exposure to manganese in scalp hair. This proposed study will advance our understanding of the neurotoxic effects of chronic manganese and arsenic exposure in children, building on a limited amount of previous work. Due to the industrial source of these contaminants in the United States, exposure to these metals could be reduced or eliminated if warranted. PUBLIC HEALTH RELEVANCE: The developing fetus and young children are particularly susceptible to environmental insults, but investigations of the effects of prenatal and early childhood exposure to most chemicals are limited and susceptible to distinct methodologic challenges. This proposed project can significantly impact the health and welfare of a vulnerable population by describing the association between two potentially preventable exposures - air pollution from manganese and arsenic- and child neurobehavioral development.